The current invention describes the preparation of a novel series of chemically bifunctional function molecules with the design purpose of improving the pharmacologic characteristics of either the vasodilator or the drug/diagnostic moiety. There are published reports suggesting that in many medical conditions related to peripheral vascular disease and neuropathy, including diabetic neuropathy, there is a compromised microcirculatory environment around the nerves, which may have an influence on the normal functions of the nerves, leading to the abnormal sensations or lack of sensations noted with these medical conditions. Improving the metabolic state in the tissue around the nerve cells in the skin through an improved blood flow, increasing the oxygenation and nutrient delivery to the tissue as well as improving the removal of cellular and tissue waste products, improves the health and functioning of the nerve cells, which in turn creates an environment for the reversal of a deteriorating medical condition or slows the rate of deterioration. The use of bifunctional function molecules, including the use of vasodilators linked to a penetration enhancer molecule would improve the delivery of these agents to the compromised tissue.
The preparation of the stable and covalently linked bifunctional molecules from components such as a vasodilator (e.g., nicotinic acid or tolazoline) linked to a penetration enhancing moiety (e.g., menthol or linoleic acid), allows for the more efficient and coordinated delivery of the active agents (i.e., drugs or vasodilators). The improved delivery of a functional drug agent or vasodilator improves the treatment of a medical condition in a manner that can be more accurately measured and predicted since the physicochemical characteristics and the temporal positioning of the molecule in the skin are better understood and defined as opposed to those associated with an unlinked or un-bonded formulation containing the same two substances.
The efficiency and the focused application of use with the present invention includes the use of a broad class of novel molecules, containing at least two types of functional characteristics, including linking a vasodilator or a drug molecule to a molecule designed to promote penetration through the skin or to another type of vasodilator. The three classes of molecules: vasodilators, penetration enhancers and drugs may be linked as combinations of vasodilator to drug; vasodilator to penetration enhancer and penetration enhancer to drug.